KasQ an Epimerase Primes the Biosynthesis of Aminoglycoside Antibiotic Kasugamycin and KasF/H Acetyltransferases Inactivate Its Activity

Rattinam, Rajesh; Basha, R. Sidick; Wang, Yung-Lin; Wang, Zhe‐Chong; Hsu, Ning-Shian; Lin, Kuan‐Hung; Zadeh, Saeid Malek; Adhikari, Kamal; Lin, Jian; Li, Tsung‐Lin

doi:10.3390/biomedicines10020212

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…Furthermore, KSM is an aminoglycoside antibiotic that exhibits considerable medical potential [5]. For example, KSM has been used to counteract some recalcitrant human diseases, such as by controlling Mycobacterium tuberculosis, inhibiting herpes simplex virus-2, and even showing promising activity reductions against COVID-19 [6]. However, KSM is sensitive to light and heat, and it is unstable under alkaline conditions.…”

Section: Introductionmentioning

confidence: 99%

Biochar and Cd Alter the Degradation and Transport of Kasugamycin in Soil and Spinach

Cui,

Ma,

Quan

et al. 2023

Agriculture

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Biochar has been widely studied to reduce multiple contaminant sources in one matrix (e.g., several heavy metals in soils), yet less attention has been paid to accelerating pesticide degradation while in the presence of any heavy metals, such as when kasugamycin (KSM) and cadmium (Cd) are both present in soil. While KSM has low toxicity compared to other pesticides, it can be a potential health risk when applied to vegetable crops, especially when KSM is used or overapplied to achieve rapid reductions in insect and disease pressure. The degradation behavior of KSM (2 kg ha−1) in the presence of Cd (20 mg kg−1) and biochar (5% by wt.) when growing spinach (Spinacia oleracea) was studied. The biochar increased spinach shoot and root biomass by 51.0–54.8% and 24.4–39.0%, respectively, compared to the KSM treatment only. Compared to the treatments that did not receive biochar, the biochar application increased the KSM degradation in the soil by 8.4–68.4% and, subsequently, less KSM was absorbed by the spinach roots (18.0–48.4%) and shoots (33.0–33.2%). The KSM degradation rate, as a function of soil depth, was enhanced in the presence of Cd. The biochar also effectively decreased the KSM concentration with soil depth, reducing downward KSM migration. The KSM degradation, increased by the biochar, led to smaller organic moieties and some macromolecular organic phases. In soils that are contaminated with Cd and where vegetables are raised, biochar may be used as an environmentally friendly proponent for increasing KSM degradation, reducing KSM downward transport and, thus, protecting environmental and human health.

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Section: Introductionmentioning

confidence: 99%

Biochar and Cd Alter the Degradation and Transport of Kasugamycin in Soil and Spinach

Cui,

Ma,

Quan

et al. 2023

Agriculture

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“…Multidisciplinary approaches effectively reveal the synthesis pathways of NPs [ 56 , 57 ] or discover new molecules that might be used as templates to develop novel biotherapeutics [ 58 , 59 ].…”

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confidence: 99%

Recent Advances in the Discovery of Novel Drugs on Natural Molecules

Quintieri,

Caputo,

Nicolotti

2024

Biomedicines

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Insights into structure and activity of a UDP-GlcNAc 2-epimerase involved in secondary cell wall polymer biosynthesis in Paenibacillus alvei

Stefanović,

Legg,

Mateyko

et al. 2024

Front. Mol. Biosci.

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IntroductionS-layer anchoring in Paenibacillus alvei is enabled by a non-covalent interaction between an S-layer homology domain trimer and a secondary cell wall polymer (SCWP), ensuring the structural integrity of the bacterial cell wall. Within the SCWP repeat, pyruvylated ManNAc serves as the ligand and the UDP-GlcNAc-2-epimerase MnaA supplies UDP-ManNAc to SCWP biosynthesis.MethodsTo better understand SCWP biosynthesis and identify strategies for inhibiting pathogens with comparable cell wall architecture, like Bacillus anthracis, MnaA and rational variants were produced in E. coli and their kinetic constants determined. The effect of UDP-GlcNAc as a predicted allosteric activator and tunicamycin as a potential inhibitor of MnaA was tested in vitro supported by molecular docking experiments. Additionally, wild-type MnaA was crystallized.ResultsWe present the crystal structure of unliganded P. alvei MnaA resolved at 2.20 Å. It adopts a GT-B fold consistent with other bacterial non-hydrolyzing UDP-GlcNAc 2-epimerases. A comparison of amino acid sequences reveals conservation of putative and known catalytic and allosteric-site residues in MnaA, which was confirmed through analysis of Q42A, Q69A, E135A and H241A MnaA variants. The kinetic parameters KM and kcat of MnaA were determined to be 3.91 mM and 33.44 s-1 for the forward, and 2.41 mM and 6.02 s-1 for the reverse reaction. While allosteric regulation by UDP-GlcNAc has been proposed as a mechanism for enzyme activation, UDP-GlcNAc was not found to be essential for UDP-ManNAc epimerization by P. alvei MnaA. However, the reaction rate doubled upon addition of 5% UDP-GlcNAc. Unexpectedly, the UDP-GlcNAc analog tunicamycin did not inhibit MnaA. Molecular docking experiments comparing tunicamycin binding of P. alvei MnaA and Staphylococcus aureus MnaA, which is inhibited by tunicamycin, revealed different residues exposed to the antibiotic excluding, those at the predicted allosteric site of P. alvei MnaA, corroborating tunicamycin resistance.ConclusionThe unliganded crystal structure of P. alvei MnaA reveals an open conformation characterized by an accessible cleft between the N- and C-terminal domains. Despite the conservation of residues involved in binding the allosteric activator UDP-GlcNAc, the enzyme is not strictly regulated by the substrate. Unlike S. aureus MnaA, the activity of P. alvei MnaA remains unaffected by tunicamycin.

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KasQ an Epimerase Primes the Biosynthesis of Aminoglycoside Antibiotic Kasugamycin and KasF/H Acetyltransferases Inactivate Its Activity

Cited by 3 publications

References 42 publications

Biochar and Cd Alter the Degradation and Transport of Kasugamycin in Soil and Spinach

Biochar and Cd Alter the Degradation and Transport of Kasugamycin in Soil and Spinach

Recent Advances in the Discovery of Novel Drugs on Natural Molecules

Insights into structure and activity of a UDP-GlcNAc 2-epimerase involved in secondary cell wall polymer biosynthesis in Paenibacillus alvei

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